Project Summary Extensive epidemiological data has documented an association between sexual violence and HIV acquisition through direct and indirect pathways. However, the underlying biological mechanism to explain this association is less understood. Sexual violence may contribute to HIV acquisition by disrupting the cervicovaginal epithelium and magnifying local inflammation and immune activation. Sexual violence may also alter the hypothalamic-pituitary-adrenal (HPA) axis resulting in changes to the innate and adaptive immune system in the female genital tract (FGT) and alterations to cervicovaginal epithelial health. When compared to adult women, adolescent girls may be at heightened biological risk due to differences in the genital mucosa such as cervical ectopy and high baseline inflammation rendering girls more vulnerable to adverse effects of stress. Our preliminary data indicate both recent and chronic cases of sexual violence cause dysregulation of critical FGT immune mediators that have the potential to affect HIV susceptibility. Establishing a better understanding of the correlation between immunity in the FGT and the dysregulated HPA axis, as well as the differences between adolescent girls and adult women is critical for the development of strategies to counter the adverse effects of sexual trauma resulting from mucosal injury in efforts to reduce the risk of HIV acquisition. To that end, we will: 1) assess the impact of sexual trauma on FGT immunity; 2) assess the impact of sexual trauma on the central and peripheral HPA axis; 3) determine the extent to which the dysregulated HPA axis affects FGT immunity following sexual trauma; and 4) examine whether risk factors linked to sexual violence (i.e., sexual risk behaviors, substance use, mental health) are associated with HPA axis dysregulation and FGT immunity in adolescent girls and adult women post-sexual trauma. We will further determine how these associations change over time following the traumatic event. Our multi-disciplinary team will conduct a case- control study with follow-up among adolescent girls aged 14-19 n=30; 15 cases and 15 controls) and adult women aged 20 and older (n=30; 15 cases and 15 controls). All participants will complete a quantitative survey and clinical assessment at baseline, 1- and 3-month follow-up visits. The proposed research will advance the FY2016 Trans-NIH Plan for HIV-related Research by ?examining the relationship of the female genital tract immune function, including genital injury due to sexual violence, to HIV risk? and is highly responsive to RFA- AI-15-058 by ?conducting research that addresses the gaps in our understanding of how reproductive maturation impacts HIV susceptibility.? Findings from this research will facilitate future hypothesis-driven longitudinal research and development of safe and efficacious biomedical prevention strategies.